title: Serum Fucosylated Haptoglobin as a Novel Diagnostic Biomarker for Predicting Hepatocyte Ballooning and Nonalcoholic Steatohepatitis.
abstract: Nonalcoholic fatty liver disease (NAFLD) is a growing medical problem around the world. NAFLD patients with nonalcoholic steatohepatitis (NASH) can develop cirrhosis and hepatocellular carcinoma. The ability to distinguish NASH from simple steatosis would be of great clinical significance. Ballooning hepatocytes are characteristic of typical pathological NASH; here, the polarized secretion of proteins is disrupted due to destruction of the cytoskeleton. We previously reported that fucosylated glycoproteins are secreted into bile, but not into sera in normal liver. Therefore, we hypothesized that the fucosylation-based sorting machinery would be disrupted in ballooning hepatocytes, and serum fucosylated glycoproteins would increase in NASH patients. To confirm our hypothesis, we evaluated serum fucosylated haptoglobin (Fuc-Hpt) levels in biopsy-proven NAFLD patients (n = 126) using a lectin-antibody ELISA kit. Fuc-Hpt levels were significantly increased in NASH patients compared with non-NASH (NAFLD patients without NASH) patients. Interestingly, Fuc-Hpt levels showed a significant stepwise increase with increasing hepatocyte ballooning scores. Multiple logistic regression analysis showed that Fuc-Hpt levels were independent and significant determinants of the presence of ballooning hepatocytes. Moreover, Fuc-Hpt levels were useful in monitoring liver fibrosis staging. Next, to investigate the significance of serum Fuc-Hpt in a larger population, we measured Fuc-Hpt levels in ultrasound-diagnosed NAFLD subjects (n = 870) who received a medical health checkup. To evaluate NAFLD disease severity, we used the FIB-4 index (based on age, serum AST and ALT levels, and platelet counts). Fuc-Hpt levels increased stepwise with increasing FIB-4 index.
  
  
  
  Measurement of serum Fuc-Hpt levels can distinguish NASH from non-NASH patients, and predict the presence of ballooning hepatocytes in NAFLD patients with sufficient accuracy. These results support the potential usefulness of measuring Fuc-Hpt levels in clinical practice.
authors.affiliation: Department of Molecular Biochemistry and Clinical Investigation, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan ; Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kamada
authors.forename: Maaya
authors.initials: M
authors.lastname: Akita
authors.forename: Yuri
authors.initials: Y
authors.lastname: Takeda
authors.forename: Shin
authors.initials: S
authors.lastname: Yamada
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sawai
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Doi
authors.forename: Hitomi
authors.initials: H
authors.lastname: Asazawa
authors.forename: Kotarosumitomo
authors.initials: K
authors.lastname: Nakayama
authors.forename: Kayo
authors.initials: K
authors.lastname: Mizutani
authors.forename: Hironobu
authors.initials: H
authors.lastname: Fujii
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yakushijin
authors.forename: Masanori
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Hisao
authors.initials: H
authors.lastname: Ezaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiramatsu
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kiso
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Imai
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D006242:Haptoglobins / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000175:diagnosis / Q000473:pathology
chemical_list: D015415:Biomarkers; C485359:HP protein, human; D006242:Haptoglobins